title: A role of the aryl hydrocarbon receptor in attenuation of colitis.
abstract: OBJECTIVE
  The aryl hydrocarbon receptor (AhR), which is a member of the basic helix-loop-helix/Per-Arnt-Sim homology superfamily, plays an important role in multiple biological functions, and AhR knockout (AhR KO) animals suffer from a variety of organ disorders including a decline in the efficacy of their immune system. In addition, AhR activation is known to aid the maintenance of homeostasis in vivo. In this study, we investigated whether AhR is functionally associated with intestinal immunity.
  
  
  RESULTS
  In in vivo experiments, it was found that dextran sodium sulfate (DSS)-evoked colitis was more severe in AhR KO mice than in C57BL/6J wild type mice. It was also revealed that the administration of DSS increased the expression levels of AhR and CYP1A1 mRNA in the colon epithelium. In addition, oral administration of β-naphthoflavone (βNF), a non-toxic agonist of AhR, suppressed the pathogenesis of DSS-induced colitis. βNF also attenuated DSS-induced colitis. In cell culture experiments, downregulation of AhR in human colon carcinoma SW480 cells enhanced the inflammatory responses evoked by lipopolysaccharide (LPS), and furthermore, AhR activation attenuated LPS-induced inflammatory responses, suggesting that AhR expressing intestinal epithelial cells are involved in the prevention of colitis.
  
  
  CONCLUSIONS
  Our findings about the potential role of AhR activators in epithelial immune regulation aid our understanding of mucosal homeostasis and inflammatory bowl disease (IBD) and suggest that AhR activation has therapeutic value for the treatment of IBD.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1, Chuo-ku, Kusunoki-cho, Kobe, Hyogo 650-0017, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Furumatsu
authors.forename: Shin
authors.initials: S
authors.lastname: Nishiumi
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kawano
authors.forename: Makoto
authors.initials: M
authors.lastname: Ooi
authors.forename: Tomoo
authors.initials: T
authors.lastname: Yoshie
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Shiomi
authors.forename: Hiromu
authors.initials: H
authors.lastname: Kutsumi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ashida
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Fujii-Kuriyama
authors.forename: Takeshi
authors.initials: T
authors.lastname: Azuma
authors.forename: Masaru
authors.initials: M
authors.lastname: Yoshida
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003092:Colitis / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D003110:Colonic Neoplasms / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D016264:Dextran Sulfate / Q000633:toxicity; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D013047:Specific Pathogen-Free Organisms; D019324:beta-Naphthoflavone / Q000494:pharmacology
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D019324:beta-Naphthoflavone; D016264:Dextran Sulfate; D004121:Dimethyl Sulfoxide